NZ537122A - Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions - Google Patents

Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions

Info

Publication number: NZ537122A
Authority: NZ; New Zealand
Prior art keywords: solvate; pharmaceutically acceptable; formula; salt; compound
Prior art date: 2002-06-14

Application number

NZ537122A

Other languages

English (en)

Inventor

Ingemar Starke

Mikael Ulf Johan Dahlstrom

Suzanne Alenfalk

Tore Skjaret

Malin Lemurell

Original Assignee

Astrazeneca Ab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-06-14

Filing date

2003-06-10

Publication date

2006-11-30

2003-06-10 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2006-11-30 Publication of NZ537122A publication Critical patent/NZ537122A/en

Links

238000011282 treatment Methods 0.000 title claims description 59
108090000765 processed proteins & peptides Proteins 0.000 title description 2
102000004196 processed proteins & peptides Human genes 0.000 title description 2
NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical group S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 166
238000004519 manufacturing process Methods 0.000 claims abstract description 35
230000002401 inhibitory effect Effects 0.000 claims abstract description 25
239000003814 drug Substances 0.000 claims abstract description 24
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
239000001257 hydrogen Substances 0.000 claims abstract description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 6
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 9
102100021711 Ileal sodium/bile acid cotransporter Human genes 0.000 claims abstract 2
101710156096 Ileal sodium/bile acid cotransporter Proteins 0.000 claims abstract 2
125000001475 halogen functional group Chemical group 0.000 claims abstract 2
150000003839 salts Chemical class 0.000 claims description 282
239000012453 solvate Substances 0.000 claims description 270
229940002612 prodrug Drugs 0.000 claims description 137
239000000651 prodrug Substances 0.000 claims description 137
241001465754 Metazoa Species 0.000 claims description 63
238000000034 method Methods 0.000 claims description 63
-1 hydroxy, methoxy Chemical group 0.000 claims description 56
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 48
239000003613 bile acid Substances 0.000 claims description 39
HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 33
230000008569 process Effects 0.000 claims description 29
239000011230 binding agent Substances 0.000 claims description 27
239000003085 diluting agent Substances 0.000 claims description 25
229940123934 Reductase inhibitor Drugs 0.000 claims description 23
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
239000008194 pharmaceutical composition Substances 0.000 claims description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 16
102000023984 PPAR alpha Human genes 0.000 claims description 16
108010028924 PPAR alpha Proteins 0.000 claims description 16
102000000536 PPAR gamma Human genes 0.000 claims description 16
108010016731 PPAR gamma Proteins 0.000 claims description 16
239000002253 acid Substances 0.000 claims description 16
239000000556 agonist Substances 0.000 claims description 16
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230000001225 therapeutic effect Effects 0.000 claims description 11
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239000002904 solvent Substances 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 9
235000019439 ethyl acetate Nutrition 0.000 claims description 8
230000002829 reductive effect Effects 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
FHGWEHGZBUBQKL-UHFFFAOYSA-N 1,2-benzothiazepine Chemical compound S1N=CC=CC2=CC=CC=C12 FHGWEHGZBUBQKL-UHFFFAOYSA-N 0.000 claims description 5
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 5
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 5
239000012317 TBTU Substances 0.000 claims description 4
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 claims description 4
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 claims description 4
BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 4
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 3
XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 3
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 3
229960005370 atorvastatin Drugs 0.000 claims description 3
230000000069 prophylactic effect Effects 0.000 claims description 3
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KJFRSZASZNLCDF-UHFFFAOYSA-N 1,5-benzothiazepine Chemical compound S1C=CC=NC2=CC=CC=C12 KJFRSZASZNLCDF-UHFFFAOYSA-N 0.000 claims description 2
DTHMTBUWTGVEFG-DDWIOCJRSA-N methyl (2r)-2-amino-2-phenylacetate;hydrochloride Chemical compound Cl.COC(=O)[C@H](N)C1=CC=CC=C1 DTHMTBUWTGVEFG-DDWIOCJRSA-N 0.000 claims 1
CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical group C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 abstract 2
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239000002552 dosage form Substances 0.000 description 26
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 14
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230000003516 hyperlipidaemic effect Effects 0.000 description 11
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
238000001727 in vivo Methods 0.000 description 9
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
125000002252 acyl group Chemical group 0.000 description 8
239000000243 solution Substances 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
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SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
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125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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Health & Medical Sciences (AREA)
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NZ537122A 2002-06-14 2003-06-10 Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions NZ537122A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0213669.5A GB0213669D0 (en)	2002-06-14	2002-06-14	Chemical compounds
PCT/GB2003/002499 WO2003106482A1 (en)	2002-06-14	2003-06-10	Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions

Publications (1)

Publication Number	Publication Date
NZ537122A true NZ537122A (en)	2006-11-30

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ID=9938564

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Application Number	Title	Priority Date	Filing Date
NZ537122A NZ537122A (en)	2002-06-14	2003-06-10	Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions

Country Status (25)

Country	Link
US (1)	US7192947B2 (de)
EP (1)	EP1515984B1 (de)
JP (1)	JP4423191B2 (de)
KR (1)	KR20050010514A (de)
CN (1)	CN1659182A (de)
AR (1)	AR039672A1 (de)
AT (1)	ATE424407T1 (de)
AU (1)	AU2003240079B2 (de)
BR (1)	BR0311628A (de)
CA (1)	CA2489463A1 (de)
DE (1)	DE60326451D1 (de)
ES (1)	ES2321826T3 (de)
GB (1)	GB0213669D0 (de)
IS (1)	IS7597A (de)
MX (1)	MXPA04012603A (de)
MY (1)	MY134270A (de)
NO (1)	NO20045099L (de)
NZ (1)	NZ537122A (de)
PL (1)	PL372626A1 (de)
RU (1)	RU2315772C2 (de)
SA (1)	SA03240217B1 (de)
TW (1)	TWI282790B (de)
UY (1)	UY27846A1 (de)
WO (1)	WO2003106482A1 (de)
ZA (1)	ZA200409860B (de)

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2002
- 2002-06-14 GB GBGB0213669.5A patent/GB0213669D0/en not_active Ceased
2003
- 2003-06-10 AU AU2003240079A patent/AU2003240079B2/en not_active Ceased
- 2003-06-10 BR BR0311628-0A patent/BR0311628A/pt not_active IP Right Cessation
- 2003-06-10 KR KR10-2004-7020341A patent/KR20050010514A/ko not_active Ceased
- 2003-06-10 EP EP03732693A patent/EP1515984B1/de not_active Expired - Lifetime
- 2003-06-10 WO PCT/GB2003/002499 patent/WO2003106482A1/en not_active Ceased
- 2003-06-10 ES ES03732693T patent/ES2321826T3/es not_active Expired - Lifetime
- 2003-06-10 AT AT03732693T patent/ATE424407T1/de not_active IP Right Cessation
- 2003-06-10 JP JP2004513313A patent/JP4423191B2/ja not_active Expired - Fee Related
- 2003-06-10 CN CN038137372A patent/CN1659182A/zh active Pending
- 2003-06-10 DE DE60326451T patent/DE60326451D1/de not_active Expired - Lifetime
- 2003-06-10 MX MXPA04012603A patent/MXPA04012603A/es active IP Right Grant
- 2003-06-10 CA CA002489463A patent/CA2489463A1/en not_active Abandoned
- 2003-06-10 US US10/518,010 patent/US7192947B2/en not_active Expired - Fee Related
- 2003-06-10 NZ NZ537122A patent/NZ537122A/en unknown
- 2003-06-10 RU RU2005100836/04A patent/RU2315772C2/ru not_active IP Right Cessation
- 2003-06-10 PL PL03372626A patent/PL372626A1/xx not_active Application Discontinuation
- 2003-06-12 TW TW092115986A patent/TWI282790B/zh not_active IP Right Cessation
- 2003-06-12 UY UY27846A patent/UY27846A1/es unknown
- 2003-06-12 MY MYPI20032191A patent/MY134270A/en unknown
- 2003-06-13 AR ARP030102120A patent/AR039672A1/es not_active Application Discontinuation
- 2003-07-27 SA SA03240217A patent/SA03240217B1/ar unknown
2004
- 2004-11-23 NO NO20045099A patent/NO20045099L/no not_active Application Discontinuation
- 2004-12-06 ZA ZA200409860A patent/ZA200409860B/en unknown
- 2004-12-15 IS IS7597A patent/IS7597A/is unknown

Also Published As

Publication number	Publication date
EP1515984B1 (de)	2009-03-04
CA2489463A1 (en)	2003-12-24
CN1659182A (zh)	2005-08-24
NO20045099L (no)	2005-01-06
TWI282790B (en)	2007-06-21
WO2003106482A1 (en)	2003-12-24
ZA200409860B (en)	2005-10-19
US7192947B2 (en)	2007-03-20
MY134270A (en)	2007-11-30
PL372626A1 (en)	2005-07-25
AU2003240079A1 (en)	2003-12-31
AR039672A1 (es)	2005-03-09
KR20050010514A (ko)	2005-01-27
MXPA04012603A (es)	2005-03-23
ES2321826T3 (es)	2009-06-12
BR0311628A (pt)	2005-03-08
ATE424407T1 (de)	2009-03-15
DE60326451D1 (de)	2009-04-16
UY27846A1 (es)	2003-12-31
JP2006506328A (ja)	2006-02-23
EP1515984A1 (de)	2005-03-23
AU2003240079B2 (en)	2007-11-15
RU2005100836A (ru)	2005-09-10
US20050222120A1 (en)	2005-10-06
IS7597A (is)	2004-12-15
GB0213669D0 (en)	2002-07-24
SA03240217B1 (ar)	2007-10-29
JP4423191B2 (ja)	2010-03-03
RU2315772C2 (ru)	2008-01-27
TW200400182A (en)	2004-01-01

Legal Events

Date	Code	Title	Description
2007-03-30	PSEA	Patent sealed
2007-04-27	RENW	Renewal (renewal fees accepted)

Publication	Publication Date	Title
AU2003240079B2 (en)	2007-11-15	Peptides derivatives comprising thiazepine group for the treatment of hyperlipidemic conditions
US7132416B2 (en)	2006-11-07	Benzothiazepine and benzothiazepine derivatives with ileal bile acid transport (IBAT) inhibotory activity for the treatment hyperlipidaemia
EP1427718B1 (de)	2006-11-15	Benzothiepine als ileal bile acid transport inhibotoren
EP1430040B1 (de)	2009-08-05	Benzothiazepinderivate
EP1427713B1 (de)	2010-01-06	Benzothiazepin-derivate für die behandlung von hyperlipidemia
US20040067933A1 (en)	2004-04-08	Chemical compounds
US20050143368A1 (en)	2005-06-30	Chemical compounds
AU2002329387A1 (en)	2003-06-19	Benzothiazepine and benzothiadiazepine derivatives with ileal bile acid transport (IBAT) inhibitory activity for the treatment hyperlipidaemia
AU2002331927A1 (en)	2003-06-19	Benzothiazepine derivatives for the treatment of hyperlipidaemia
HK1065258B (en)	2007-06-08	Benzothiazepine and benzothiadiazepine derivatives with ileal bile acid transport (ibat) inhibitory activity for the treatment hyperlipidaemia
AU2002321579A1 (en)	2003-03-18	Benzothiazepine derivatives
AU2002329386A1 (en)	2003-03-24	Benzothiepine ileal bile acid transport inhibitors